| 11. |
- Ribi, Karin, et al.
(author)
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Quality of life under extended continuous versus intermittent adjuvant letrozole in lymph node-positive, early breast cancer patients: the SOLE randomised phase 3 trial.
- 2019
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In: British journal of cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 120, s. 959-967
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Journal article (peer-reviewed)abstract
- In the phase III SOLE trial, the extended use of intermittent versus continuous letrozole for 5 years did not improve disease-free survival in postmenopausal women with hormone receptor-positive breast cancer. Intermittent therapy with 3-month breaks may be beneficial for patients' quality of life (QoL).In the SOLE QoL sub-study, 956 patients completed the Breast Cancer Prevention Trial (BCPT) symptom and further QoL scales up to 24 months after randomisation. Differences in change of QoL from baseline between the two administration schedules were tested at 12 and 24 months using repeated measures mixed-models. The primary outcome was change in hot flushes at 12 months.There was no difference in hot flushes at 12 months between the two schedules, but patients receiving intermittent letrozole reported significantly more improvement at 24 months. They also indicated less worsening in vaginal problems, musculoskeletal pain, sleep disturbance, physical well-being and mood at 12 months. Overall, 25-30% of patients reported a clinically relevant worsening in key symptoms and global QoL.Less symptom worsening was observed during the first year of extended treatment with the intermittent administration. For women experiencing an increased symptom burden of extended adjuvant endocrine therapy, an intermittent administration is a safe alternative.Clinical trial information: NCT00651456.
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| 12. |
- Shu, Xiang, et al.
(author)
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Associations of obesity and circulating insulin and glucose with breast cancer risk : a Mendelian randomization analysis
- 2019
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In: International Journal of Epidemiology. - : OXFORD UNIV PRESS. - 0300-5771 .- 1464-3685. ; 48:3, s. 795-806
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Journal article (peer-reviewed)abstract
- Background: In addition to the established association between general obesity and breast cancer risk, central obesity and circulating fasting insulin and glucose have been linked to the development of this common malignancy. Findings from previous studies, however, have been inconsistent, and the nature of the associations is unclear. Methods: We conducted Mendelian randomization analyses to evaluate the association of breast cancer risk, using genetic instruments, with fasting insulin, fasting glucose, 2-h glucose, body mass index (BMI) and BMI-adjusted waist-hip-ratio (WHRadj BMI). We first confirmed the association of these instruments with type 2 diabetes risk in a large diabetes genome-wide association study consortium. We then investigated their associations with breast cancer risk using individual-level data obtained from 98 842 cases and 83 464 controls of European descent in the Breast Cancer Association Consortium. Results: All sets of instruments were associated with risk of type 2 diabetes. Associations with breast cancer risk were found for genetically predicted fasting insulin [odds ratio (OR) = 1.71 per standard deviation (SD) increase, 95% confidence interval (CI) = 1.26-2.31, p = 5.09 x 10(-4)], 2-h glucose (OR = 1.80 per SD increase, 95% CI = 1.3 0-2.49, p = 4.02 x 10(-4)), BMI (OR = 0.70 per 5-unit increase, 95% CI = 0.65-0.76, p = 5.05 x 10(-19)) and WHRadj BMI (OR = 0.85, 95% CI = 0.79-0.91, p = 9.22 x 10(-6)). Stratified analyses showed that genetically predicted fasting insulin was more closely related to risk of estrogen-receptor [ER]-positive cancer, whereas the associations with instruments of 2h glucose, BMI and WHRadj BMI were consistent regardless of age, menopausal status, estrogen receptor status and family history of breast cancer. Conclusions: We confirmed the previously reported inverse association of genetically predicted BMI with breast cancer risk, and showed a positive association of genetically predicted fasting insulin and 2-h glucose and an inverse association of WHRadj BMI with breast cancer risk. Our study suggests that genetically determined obesity and glucose/insulin-related traits have an important role in the aetiology of breast cancer.
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| 13. |
- Van Belle, Vanya M. C. A., et al.
(author)
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A Mathematical Model for Interpretable Clinical Decision Support with Applications in Gynecology
- 2012
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:3
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Journal article (peer-reviewed)abstract
- Background: Over time, methods for the development of clinical decision support (CDS) systems have evolved from interpretable and easy-to-use scoring systems to very complex and non-interpretable mathematical models. In order to accomplish effective decision support, CDS systems should provide information on how the model arrives at a certain decision. To address the issue of incompatibility between performance, interpretability and applicability of CDS systems, this paper proposes an innovative model structure, automatically leading to interpretable and easily applicable models. The resulting models can be used to guide clinicians when deciding upon the appropriate treatment, estimating patient-specific risks and to improve communication with patients. Methods and Findings: We propose the interval coded scoring (ICS) system, which imposes that the effect of each variable on the estimated risk is constant within consecutive intervals. The number and position of the intervals are automatically obtained by solving an optimization problem, which additionally performs variable selection. The resulting model can be visualised by means of appealing scoring tables and color bars. ICS models can be used within software packages, in smartphone applications, or on paper, which is particularly useful for bedside medicine and home-monitoring. The ICS approach is illustrated on two gynecological problems: diagnosis of malignancy of ovarian tumors using a dataset containing 3,511 patients, and prediction of first trimester viability of pregnancies using a dataset of 1,435 women. Comparison of the performance of the ICS approach with a range of prediction models proposed in the literature illustrates the ability of ICS to combine optimal performance with the interpretability of simple scoring systems. Conclusions: The ICS approach can improve patient-clinician communication and will provide additional insights in the importance and influence of available variables. Future challenges include extensions of the proposed methodology towards automated detection of interaction effects, multi-class decision support systems, prognosis and high-dimensional data.
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| 14. |
- Van Calster, Ben, et al.
(author)
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Discrimination between benign and malignant adnexal masses by specialist ultrasound examination versus serum CA-125
- 2007
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 99:22, s. 1706-1714
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Journal article (peer-reviewed)abstract
- Background Subjective evaluation of gray-scale and Doppler ultrasound findings (i. e., pattern recognition) by an experienced examiner and preoperative serum levels of CA-125 can both discriminate benign from malignant adnexal ( i. e., ovarian, paraovarian, or tubal) masses. We compared the diagnostic performance of these methods in a large multicenter study. Methods In a prospective multicenter study-the International Ovarian Tumor Analysis-1066 women with a persistent adnexal mass underwent transvaginal gray-scale and color Doppler ultrasound examinations by an experienced examiner within 120 days of surgery. Pattern recognition was used to classify a mass as benign or malignant. Of these women, 809 also had blood collected preoperatively for measurement of serum CA-125. Various levels of CA-125 were used as cutoffs to classify masses. Results from both assays were then compared with histologic findings after surgery. Results Pattern recognition correctly classified 93% (95% confidence interval [CI]=90.9% to 94.6%) of the tumors as benign or malignant. Serum CA-125 correctly classified at best 83% ( 95% CI=80.3% to 85.6%) of the masses. Histologic diagnoses that were most often misclassified by CA-125 were fibroma, endometrioma, and abscess ( false-positive results) and borderline tumor ( false-negative results). Pattern recognition correctly classified 86% ( 95% CI=81.1% to 90.4%) of masses of these four histologic types as being benign or malignant, whereas a serum CA-125 at a cutoff of 30 U/mL correctly classified 41% ( 95% CI=34.4% to 47.5%) of them. Pattern recognition assigned a correct specific histologic diagnosis to 333 (59%, 95% CI=54.5% to 62.8%) of the 567 benign lesions. Conclusion Pattern recognition was superior to serum CA-125 for discrimination between benign and malignant adnexal masses.
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| 15. |
- Viale, Giuseppe, et al.
(author)
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Prognostic and predictive value of centrally reviewed Ki-67 labeling index in postmenopausal women with endocrine-responsive breast cancer: results from Breast International Group Trial 1-98 comparing adjuvant tamoxifen with letrozole.
- 2008
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In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 1527-7755. ; 26:34, s. 5569-75
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Journal article (peer-reviewed)abstract
- PURPOSE: To evaluate the prognostic and predictive value of Ki-67 labeling index (LI) in a trial comparing letrozole (Let) with tamoxifen (Tam) as adjuvant therapy in postmenopausal women with early breast cancer. PATIENTS AND METHODS: Breast International Group (BIG) trial 1-98 randomly assigned 8,010 patients to four treatment arms comparing Let and Tam with sequences of each agent. Of 4,922 patients randomly assigned to receive 5 years of monotherapy with either agent, 2,685 had primary tumor material available for central pathology assessment of Ki-67 LI by immunohistochemistry and had tumors confirmed to express estrogen receptors after central review. The prognostic and predictive value of centrally measured Ki-67 LI on disease-free survival (DFS) were assessed among these patients using proportional hazards modeling, with Ki-67 LI values dichotomized at the median value of 11%. RESULTS: Higher values of Ki-67 LI were associated with adverse prognostic factors and with worse DFS (hazard ratio [HR; high:low] = 1.8; 95% CI, 1.4 to 2.3). The magnitude of the treatment benefit for Let versus Tam was greater among patients with high tumor Ki-67 LI (HR [Let:Tam] = 0.53; 95% CI, 0.39 to 0.72) than among patients with low tumor Ki-67 LI (HR [Let:Tam] = 0.81; 95% CI, 0.57 to 1.15; interaction P = .09). CONCLUSION: Ki-67 LI is confirmed as a prognostic factor in this study. High Ki-67 LI levels may identify a patient group that particularly benefits from initial Let adjuvant therapy.
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| 16. |
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